Related Experiment Video

Updated: Jul 3, 2026

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

Necrotic cell death and 'necrostatins': now we can control cellular explosion

Peter Vandenabeele1, Wim Declercq, Tom Vanden Berghe

  • 1Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium. Peter.Vandenabeele@dmbr.UGent.be

Trends in Biochemical Sciences
|July 19, 2008
PubMed

Insights

Receptor-interacting protein 1 (RIP1) kinase activity drives necrotic cell death. New necrostatin drugs block this RIP1 activity, revealing necrosis as a controlled process and offering tools for disease research.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of cell death
  • Biochemistry

Background:

  • Receptor-interacting protein 1 (RIP1) kinase is crucial for death-receptor-induced necrotic cell death.
  • Necrostatin compounds have emerged as inhibitors of RIP1 kinase activity.
  • This inhibition effectively blocks tumor necrosis factor-induced necrotic cell death.

Purpose of the Study:

  • To explore the role of RIP1 kinase activity in programmed necrosis.
  • To investigate the therapeutic potential of necrostatins in blocking necrotic cell death.
  • To establish necrosis as a regulated cellular process comparable to apoptosis.

Main Methods:

  • Utilizing necrostatin compounds to inhibit RIP1 kinase activity.
  • Investigating the effects of RIP1 inhibition on tumor necrosis factor signaling pathways.
  • Analyzing the contribution of necrotic cell death in experimental disease models.

Main Results:

  • Necrostatin treatment successfully inhibited RIP1 kinase activity.
  • This inhibition blocked tumor necrosis factor-induced necrotic cell death.
  • The findings support the concept of receptor-induced necrosis as a controlled cellular mechanism.

Conclusions:

  • RIP1 kinase activity is essential for initiating necrotic cell death.
  • Necrostatins are effective inhibitors of RIP1 kinase, blocking necrosis.
  • Necrosis is a regulated cellular process, and necrostatins are valuable tools for studying its role in diseases.

More Related Videos

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis08:55

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

Related Concept Videos

Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Cellular Injury IlI: Cellular Death01:11

Cellular Injury IlI: Cellular Death

Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...